Dialysis treatment devices for removing urea

ABSTRACT

Dialysis treatment devices and methods for removing urea from dialysis waste streams are provided. In a general embodiment, the present disclosure provides a dialysis treatment device including: 1) a first filter having a filtration membrane, 2) a urea removal unit having urease and in fluid communication with the first filter, and 3) a second filter having an ion rejection membrane and in fluid communication with the first filter and the urea removal unit.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/296,522 filed Nov. 15, 2011, which is a divisional of U.S. patentapplication Ser. No. 12/482,869 filed Jun. 11, 2009, the entire contentsof which are herein incorporated by reference in their entirety.

BACKGROUND

The present disclosure is in the general field of dialysis treatmentdevices and methods, and in particular, for removing urea from dialysiswaste streams.

Hemodialysis and peritoneal dialysis are two types of dialysis therapiesused commonly to treat loss of kidney function. A hemodialysis treatmentutilizes the patient's blood to remove waste, toxins and excess waterfrom the patient. The patient is connected to a hemodialysis machine andthe patient's blood is pumped through the machine. Catheters areinserted into the patient's veins and arteries so that blood can flow toand from the hemodialysis machine. The blood passes through a dialyzerof the machine, which removes waste, toxins and excess water from theblood. The cleaned blood is returned to the patient. A large amount ofdialysate, for example about 120 liters, is consumed to dialyze theblood during a single hemodialysis therapy. Hemodialysis treatment lastsseveral hours and is generally performed in a treatment center aboutthree or four times per week.

Peritoneal dialysis uses a dialysis solution, also called dialysate,which is infused into a patient's peritoneal cavity via a catheter. Thedialysate contacts the peritoneal membrane of the peritoneal cavity.Waste, toxins and excess water pass from the patient's bloodstream,through the peritoneal membrane and into the dialysate due to diffusionand osmosis, i.e., an osmotic gradient occurs across the membrane. Thespent dialysate is drained from the patient, removing waste, toxins andexcess water from the patient. This cycle is repeated.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), tidal flow APD and continuous flow peritoneal dialysis(“CFPD”). CAPD is a manual dialysis treatment. The patient manuallyconnects an implanted catheter to a drain, allowing spent dialysatefluid to drain from the peritoneal cavity. The patient then connects thecatheter to a bag of fresh dialysate, infusing fresh dialysate throughthe catheter and into the patient. The patient disconnects the catheterfrom the fresh dialysate bag and allows the dialysate to dwell withinthe peritoneal cavity, wherein the transfer of waste, toxins and excesswater takes place. After a dwell period, the patient repeats the manualdialysis procedure, for example, four times per day, each treatmentlasting about an hour. Manual peritoneal dialysis requires a significantamount of time and effort from the patient, leaving ample room forimprovement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialysate and to a fluid drain. APD machines pump freshdialysate from a dialysate source, through the catheter, into thepatient's peritoneal cavity, and allow the dialysate to dwell within thecavity, and allow the transfer of waste, toxins and excess water to takeplace. The source can be multiple sterile dialysate solution bags.

APD machines pump spent dialysate from the peritoneal cavity, though thecatheter, to the drain. As with the manual process, several drain, filland dwell cycles occur during APD. A “last fill” occurs at the end ofCAPD and APD, which remains in the peritoneal cavity of the patientuntil the next treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all of the fluid from the patient over alonger period of time, a portion of the fluid is removed and replacedafter smaller increments of time.

Continuous flow, or CFPD, dialysis systems clean or regenerate spentdialysate instead of discarding it. The systems pump fluid into and outof the patient, through a loop. Dialysate flows into the peritonealcavity through one catheter lumen and out another catheter lumen. Thefluid exiting the patient passes through a reconstitution device thatremoves waste from the dialysate, e.g., via a urea removal column thatemploys urease to enzymatically convert urea into ammonia (e.g. ammoniumcation). The ammonia is then removed from the dialysate by adsorptionprior to reintroduction of the dialysate into the peritoneal cavity.Additional sensors are employed to monitor the removal of ammonia. CFPDsystems are typically more complicated than batch systems.

In both hemodialysis and peritoneal dialysis, “sorbent” technology canbe used to remove uremic toxins from waste dialysate, re-injecttherapeutic agents (such as ions and/or glucose) into the treated fluid,and reuse that fluid to continue the dialysis of the patient. Onecommonly used sorbent is made from zirconium phosphate, which is used toremove ammonia generated from the hydrolysis of urea. Typically, a largequantity of sorbent is necessary to remove the ammonia generated duringdialysis treatments.

The main advantage of the sorbent based approach is that very lowvolumes of water are required to achieve high volume dialysistreatments. The main disadvantage of the sorbent system is the high costof the sorbent disposable, the amount of space required to house thesorbent, and concerns regarding the purity of the recycled solution, asmany ions remain in the fluid after treatment and verification of purityis technically challenging to perform.

SUMMARY

The present disclosure provides dialysis treatment devices and methodsthat treat dialysis waste streams during hemodialysis and peritonealdialysis. In a general embodiment, the present disclosure provides adialysis treatment device including: 1) a first filter having afiltration membrane, 2) a urea removal unit having urease and in fluidcommunication with the first filter, and 3) a second filter having anion rejection membrane and in fluid communication with the first filterand the urea removal unit.

In an embodiment, the dialysis treatment device includes a flowrestrictor positioned between the first filter and the second filter.The dialysis treatment device can be contained within a cartridge for awearable kidney. The cartridge can be configured to be removable and/ordisposable.

In a further alternative embodiment, the present disclosure provides adialysis treatment device including: 1) a filter having an adsorptionlayer, a filtration membrane and an ion exchange sorbent, and 2) a urearemoval unit in fluid communication with the filter. The urease removalunit can include a urease layer, an ammonia sorbent layer and an ionrejection membrane.

It is accordingly an advantage of the present disclosure to provide animproved dialysis treatment device.

It is another advantage of the present disclosure to provide an improvedurea removal cartridge.

It is yet another advantage of the present disclosure to provide asorbentless urea removal cartridge for a wearable kidney.

Still further, it is an advantage of the present disclosure to provide aurea removal cartridge for a wearable kidney having a reduced ammoniasorbent requirement.

Another advantage of the present disclosure to provide an improvedmethod for removing urea from a dialysis waste stream.

Additional features and advantages are described herein, and will beapparent from the following Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic illustration of a dialysis treatment device usingmultiple filters in an embodiment of the present disclosure.

FIG. 2 is a schematic illustration of a dialysis treatment device in athird embodiment of the present disclosure.

FIGS. 3A to 3D are schematic illustrations of the dialysis treatmentdevices used in various dialysis treatment technologies.

DETAILED DESCRIPTION

The present disclosure relates to dialysis treatment devices and methodsfor removing urea from dialysis waste streams during hemodialysis orperitoneal dialysis. In a general embodiment, the dialysis treatmentdevices are constructed and arranged to require no sorbents for trappingammonia generated by the hydrolysis of urea by urease. In anotherembodiment, the dialysis treatment devices are constructed and arrangedto significantly reduce the amount of sorbent necessary for removingurea from the dialysis waste stream. This can significantly reduce thecost, size and complexity of dialysis treatments systems that removeurea.

The dialysis treatment devices and methods can be used and implementedin various hemodialysis and peritoneal dialysis technologies such as,for example, those described in U.S. Pat. Nos. 5,244,568, 5,350,357,5,662,806, 6,592,542 and 7,318,892, which are incorporated herein byreference. The hemodialysis and peritoneal dialysis technologies can bedesigned and configured for medical centers and be implemented withon-site or at-home dialysis treatments. The dialysis treatment devicesand methods can further be used in portable dialysis treatment devicessuch as, for example, wearable artificial kidneys in which a patient maymove freely during dialysis. Non-limiting examples of portable dialysistreatment devices are described in U.S. Pat. Nos. 5,873,853, 5,984,891and 6,196,992 and U.S. Patent Publication Nos. 2007/0213665 and2008/0051696, which are incorporated herein by reference.

Referring now to the drawings and in particular to FIG. 1, oneembodiment of a dialysis treatment device 10 of the present disclosureis illustrated. Dialysis treatment device 10 includes a first filter 20,a urea removal unit 30, and a second filter 40. In this configuration,urea removal unit 20 is a separate component from the filters. Dialysistreatment device 10 can further include a constriction partition or flowrestrictor 50 positioned between first filter 20 and second filter 40.Dialysis treatment device 10 can be sized and configured to be containedwithin a treatment cartridge for a portable dialysis treatment devicessuch as, for example, wearable kidneys. The treatment cartridge in suchcases can be disposable or reusable.

First filter 20 has a filtration membrane 22. Filtration membrane 22 canbe, for example, in the form of a hollow fiber cartridge with a membraneskin. The membrane can designed to allow very small molecules (e.g.urea) to pass through while retaining charged and larger molecules.Suitable membranes that can be used as filtration membrane 22 includenanofiltration membranes or reverse osmosis membranes. An example of ananofiltration membrane is described in WO Publication No. 2004/009158,which is incorporated herein by reference. In addition, an ion coatingcan be added to nanofiltration membranes or reverse osmosis membranesused as filtration membrane 22 to further trap or exchange ioniccompounds in the dialysis waste stream.

In another embodiment, filtration membrane 22 of first filter 20 is acation rejection membrane or anion rejection membrane. Ion-rejectionmembrane 22 can be designed to allow the passage of negatively chargedions and nonionic species, but restrict the passage of specificpositively charged ions. Alternatively, ion-rejection membrane 22 canallow the passage of positively charged ions and nonionic species, butrestrict the passage of specific negatively charged ions.

Urea removal unit 30 contains urease, an enzyme that catalyzes thehydrolysis of urea into carbon dioxide (e.g. bicarbonate) and ammonia(e.g. ammonium cation). Urea from the dialysis waste stream is exposedto the urease at this location. The urease can be contained in urearemoval unit 30 in any suitable manner. For example, the urease can beimmobilized in a layer of beads or resins or be cross-linked ureaseenzyme crystals impregnated as part of a membrane. Urea removal unit 30is in fluid communication with first filter 20 via a flow path 32. Flowpath 32, and indeed any of the flow paths described herein, can beprovided as a length of tubing or as a flow path defined in a rigidand/or flexible, disposable or reusable cassette.

In an alternative embodiment, urea removal unit 20 can be integral withfirst filter 20. For example, immobilized urease can be placed outsidethe hollow fibers of ion rejection membrane 22.

Second filter 40 has an ion rejection membrane 42 and is in fluidcommunication with first filter 20 via a flow path 26 and urea removalunit 30 via a flow path 36. In different embodiments, ion rejectionmembrane 42 of second filter 40 can be a cation rejection membrane or ananion rejection membrane. In another embodiment, ion rejection membrane42 of second filter 40 is a reverse osmosis membrane.

In an alternative embodiment, dialysis treatment device 10 includes anadsorption or carbon chamber 80 in fluid communication with first filter20. In this manner, organic toxins of the dialysis waste stream can beremoved from the waste stream prior to entering first filter 20 throughadsorption onto an adsorption layer surface of the carbon (e.g.,activated carbon or other appropriate organic neutralizing surface).

In another embodiment, dialysis treatment device 10 includes asupplementary ammonia sorbent unit 90 in fluid communication with secondfilter 40 as a precautionary measure to completely remove any ammoniafrom the fluid that passes through dialysis treatment device 10. Theammonia sorbent unit can include, for example, zirconium phosphate totrap any residual ammonia in the treated fluid stream.

As seen in FIG. 1, a pump 60 causes a fluid flow path 12 of spentdialysis or a dialysis waste stream from a patient to enter first filter20 via a flow path 24. The dialysis waste stream may or may not havebeen treated, for example, using activated carbon prior to enteringdialysis treatment device 10. A pump 70 transports fluid from firstfilter 20 to urea removal unit 30 via flow paths 32 and 34. Filtrationmembrane 22 may be capable of retaining charged species such as Ca²⁺,Mg²⁺, Na⁺ and proteins within first filter 20, which flow into secondfilter 40 via flow path 26. As a result, a fluid stream composedprimarily of water and urea flows to urea removal unit 30.

Urea removal unit 30 converts urea to ammonia and carbon dioxide, whichtravel to second filter 40 via flow path 36. Second filter 40 canprovide a hollow fiber cation rejection membrane as ion rejectionmembrane 42. As a result, the ammonia remains trapped outside of ionrejection membrane 42 and does not proceed through flow path 28. Toimprove the treatment capacity of dialysis treatment device 10, flowpath 36 between urea removal unit 30 and second filter 40 should besufficiently long enough to prevent the urease contained in urea removalunit 30 from being saturated with ammonia.

The final treated dialysate stream exits second filter 40 via flow path28 for further use or treatment (e.g., ion exchange) and then back tothe patient. In addition, ions and/or fluids can be replaced in thestream, for example, through the addition of concentrated dialysiscomponents such as osmotic agents (e.g., dextrose, icodextrin, glucosepolymers, glucose polymer derivatives, amino acids), buffers (e.g.,lactate, bicarbonate) and electrolytes (e.g., sodium, potassium,calcium, magnesium) from a suitable fluid source.

In an alternative embodiment, flow restrictor 50 and/or pump 70 can beused to create high pressure gradients in first filter 20 and/or secondfilter 40. In this regard, flow restrictor 50 and/or pumps 60 and 70 canprovide a sufficiently high pressure to force fluid through filtrationmembrane 22 and out of first filter 20 via flow paths 32 and 34.

In another embodiment illustrated in FIG. 2, a dialysis treatment device100 includes a filter 110 and a urea removal unit 120 in fluidcommunication with filter 110 via flow paths 142 and 144. A pump 130 canbe positioned between filter 110 and urea removal unit 120 to facilitateflow between the two components. Dialysis treatment device 100 can besized and configured to be contained within a treatment cartridge forany of the above-listed type of dialysis treatment devices.

Filter 110 can include an adsorption layer 112, a filtration membrane114 and an ion exchange sorbent 116. Adsorption layer 112 can be, forexample, carbon. In this manner, organic toxins of the dialysis wastestream can be removed from the waste stream through adsorption onto theadsorption layer surface.

Filtration membrane 114 can be, for example, in the form of a hollowfiber cartridge with a membrane skin that is designed to allow verysmall molecules to pass through while retaining charged and largermolecules. Suitable membranes that can be used as filtration membrane114 include nanofiltration membranes or reverse osmosis membranes.Alternatively, filtration membrane 114 of filter 110 can be a cationrejection membrane or an anion rejection membrane. In an embodiment, ionexchange sorbent 116 is an anion exchange sorbent to remove anions suchas, for example, phosphate and sulfate.

Urea removal unit 120 can include a urease layer 122, an ammonia sorbentlayer 124 and an ion rejection membrane 126. Ion rejection membrane 126can be a cation rejection membrane. The urease can be contained in urearemoval unit 120 in any suitable manner. As illustrated in FIG. 2, thetreated dialysis fluid from urea removal unit 120 in flow path 146 cancombine with the treated dialysate fluid from filter 110 in flow path140 to form a combined treated fluid flow path 150 for subsequenttreatment/recirculation. In another embodiment, ion rejection membrane126 is a reverse osmosis membrane.

In an alternative embodiment, dialysis treatment device 100 includes anadsorption or carbon chamber 160 in fluid communication with filter 110.In this manner, organic toxins of the dialysis waste stream can beremoved from the waste stream prior to entering filter 110 throughadsorption onto an adsorption layer surface of the carbon (e.g.,activated carbon or other appropriate organic neutralizing surface).

In another embodiment, dialysis treatment device 100 includes asupplementary ammonia sorbent unit 170 in fluid communication with atleast one of filter 110 and urea removal unit 120 as a precautionarymeasure to completely remove any ammonia from the fluid that passesthrough dialysis treatment device 100. Ammonia sorbent unit 170 caninclude, for example, zirconium phosphate to trap any residual ammoniain the treated fluid stream.

Due to the design of dialysis treatment devices 10 and 100, sorbentssuch as zirconium phosphate, zirconium bicarbonate and/or ion exchangelayers typically used for ammonia removal may be unnecessary.Alternatively, dialysis treatment devices 10 and 100 allow for a reducedamount of sorbent necessary as compared to typical dialysis treatmentsystems using sorbents for ammonia removal.

Any of the dialysis treatment devices 10 and 100 discussed herein can beused for peritoneal dialysis (“PD”), hemodialysis (“HD”), hemofiltration(“HF”) or hemodiafiltration (“HDF”) as shown in FIGS. 3A-3D,respectively. FIG. 3A illustrates a schematic of a PD treatment beingperformed on a patient 200. Spent dialysis fluid from patient 200 entersone of dialysis treatment devices 10 and 100 for treatment/urea removal.Regenerated dialysis is returned to the patient for reuse. This can bedone on a continuous basis (“CFPD”), on a batch basis in which dialysisfluid dwells within patient 200 for a period of time, or on asemi-continuous or tidal basis.

FIG. 3B illustrates a schematic of an HD treatment being performed onpatient 200. Blood from patient 200 is pumped through a dialyzer 202,cleaned and returned to patient 200. Spent dialysis fluid from dialyzer202 is sent to one of the dialysis treatment device 10 or 100 fortreatment/urea removal. The treated fluid is then returned to dialyzer202 on a continuous basis to continuously clean the patients' blood.

FIG. 3C illustrates a schematic of an HF treatment technology. HF is atechnology similar to HD. With hemofiltration, dialysate is not used.Instead, a positive hydrostatic pressure drives water and solutes acrossthe filter membrane of hemofilter 203 from its blood compartment to itsfiltrate compartment, from which it is drained. The spent dialysis fluidis sent to one of the dialysis treatment devices 10 or 100 fortreatment/urea removal. The treated fluid is then further purified bybeing sent through one or more pyrogen filters 204 such as anultrafilter, pyrogen filter or nanofilter that removes toxins andendotoxins. The resulting replacement fluid is pumped directly into theblood causing a corrective cleansing of the patient. As with PD and HD,a net volume of fluid is taken out of the patient as ultrafiltrate toremove excess water that the patient has accumulated between treatments.

FIG. 3D illustrates a schematic of an HDF treatment technology. HDF is acombination of HD and HF. Blood is pumped through the blood compartmentof dialyzer 202 in a manner similar to HD and HF. A high rate ofultrafiltration is used, so there is a high rate of movement of waterand solutes from the blood to the dialysate that is replaced by a returnof cleansed dialysate dialyzer 202 and substitution fluid that isinfused again through one or more of a pyrogen filter, nanofilter, orultrafilter directly into the patient's blood line. HDF results in goodremoval of both large and small molecular weight solutes. Treatmentdevices 10 and 100 regenerate spent fluid from dialyzer 202 for bothdelivery back to dialyzer 202 and to the patient's blood line directlyvia ultrafilter 204.

In alternative embodiments, the present disclosure provides methodscomprising circulating a dialysis fluid in a fluid circuit of a dialysistechnology or apparatus incorporating one or more of the dialysisdevices in the form of a sorbentless or reduced sorbent cartridge. Thedialysis apparatus can be a wearable dialysis device.

The spent dialysis fluid contains wastes from a treated patient. Thespent dialysis fluid can be sent to the dialysis technology and wastessuch as urea are removed using the cartridge. The treated fluid can thenbe recirculated back to the patient for further use.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

The invention is claimed as follows:
 1. A method for removing urea froma dialysis fluid, the method comprising: circulating the dialysis fluidin a fluid circuit that includes a dialysis apparatus having cartridgecomprising 1) a first filter comprising a filtration membrane, 2) a urearemoval unit comprising urease and in fluid communication with afiltrate stream of the first filter, 3) a second filter comprising anion rejection membrane and receiving at least one of the filtrate streamof the first filter and a filtrate stream of the urea removal unit, and4) a flow restrictor positioned between the first filter and the secondfilter; removing urea from the dialysis fluid with the cartridge; andrecirculating a filtrate stream of the second filter back to patient. 2.The method of claim 1, wherein the filtration membrane is selected fromthe group consisting of a nanofiltration membrane, a reverse osmosismembrane, an ion rejection membrane, and combinations thereof.
 3. Themethod of claim 1, wherein the filtration membrane and the ion rejectionmembrane each comprise a cation rejection membrane.
 4. The method ofclaim 1, wherein the dialysis apparatus is contained within a cartridgefor a wearable kidney.
 5. The method of claim 1 further comprisingtransporting the filtrate stream of the first filter to the urea removalunit.
 6. The method of claim 1, wherein a flow path between the urearemoval unit and the second filter is sufficiently long to prevent theurease from being saturated with ammonia.
 7. The method of claim 1further comprising treating the dialysis fluid using an activated carbonunit prior to entering the dialysis apparatus.
 8. The method of claim 1,wherein the ion rejection membrane is a reverse osmosis membrane.
 9. Themethod of claim 1 further comprising trapping residual ammonia in thefiltrate stream of the second filter using a zirconium phosphate layer.10. The method of claim 1, wherein the second filter receives filtratestreams of the first filter and the urea removal unit.
 11. A method forremoving urea from a dialysis fluid, the method comprising: circulatingthe dialysis fluid in a fluid circuit that includes a dialysis apparatushaving cartridge comprising 1) a filter comprising an adsorption layer,a filtration membrane, and an ion exchange sorbent, and 2) a urearemoval unit in fluid communication with a filtrate stream of thefilter, the urea removal unit comprising a urease layer, an ammoniasorbent layer and an ion rejection membrane; removing urea from thedialysis fluid with the cartridge; and recirculating filtrate streams ofthe filter and the urea removal unit back to the patient.
 12. The methodof claim 11, wherein the filtration membrane is selected from the groupconsisting of a nanofiltration membrane, a reverse osmosis membrane, anion rejection membrane, and combinations thereof.
 13. The method ofclaim 11, wherein the dialysis apparatus is contained within a cartridgefor a wearable kidney.
 14. The method of claim 11, wherein the ionexchange sorbent is an anion exchange sorbent, and wherein the ionrejection membrane is a cation rejection membrane or a reverse osmosismembrane.
 15. The method of claim 14, wherein the reverse osmosismembrane includes an ion coating to trap ionic compounds.
 16. The methodof claim 11 further comprising transporting the filtrate stream of thefilter to the urea removal unit.
 17. The method of claim 11 furthercomprising treating the dialysis fluid using an activated carbon unitprior to entering the dialysis apparatus.
 18. The method of claim 11further comprising trapping residual ammonia in the filtrate stream ofat least one of the filter and the urea removal unit.
 19. The method ofclaim 11 further comprising trapping residual ammonia in the filtratestream of the urea removal unit.
 20. The method of claim 11, wherein thedialysis fluid is circulated through the filter via a first flow pathand through the urea removal unit via a second flow path, and whereinthe first and second flow paths combine in a third flow path to form acombined treated fluid for subsequent treatment and/or recirculation.